Proof-of-concept randomized phase II non-inferiority trial of simple versus type B2 hysterectomy in early-stage cervical cancer ≤2 cm (LESSER)

Abstract

Objective: To evaluate the non-inferiority and safety of simple hysterectomy in early stage (<2 cm) cervical cancer.

Methods: This proof-of-concept randomized phase II non-inferiority trial was performed between May 2015 and April 2018 in three oncological centers in Northeast Brazil. Patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stages IA2-IB1 cervical cancer and tumors ≤2 cm were treated with either simple or modified radical hysterectomy (Querleu-Morrow type B2). Intention-to-treat analysis was carried out. The primary endpoint was 3-year disease-free survival and secondary endpoints were overall survival, operative outcomes, adjuvant therapy, and patient's health-related quality of life (QoL).

Results: A total of 40 patients underwent either simple hysterectomy (n=20) or modified radical hysterectomy (n=20). All patients except three underwent open procedures (n=37/40, 92.5%). At a median follow-up of 52.1 months (IQR 43.9-60.1), 3-year disease-free survival was 95% (95% CI 68% to 99%) after simple hysterectomy and 100% (95% CI 100% to 100%) after modified radical hysterectomy (log-rank p=0.30). The corresponding 5-year overall survival rates were 90% (95% CI 64% to 97%) and 91% (95% CI 50% to 98%), respectively (log-rank p=0.46). The operative time was shorter after simple hysterectomy than after modified radical hysterectomy (150 min (IQR 137.5-180) vs 199.5 min (IQR 140-230); p=0.003), with a trend towards a longer time for vesical catheterization removal (1 day (IQR 1-1) vs 1 day (IQR 1-2); p=0.043). There was no post-operative mortality and the rates of post-operative complications were not statistically different between arms (15% and 25%; p=0.69). QoL questionnaires were received from only 17 patients (42.5%), with no major differences observed over time between the surgical arms.

Conclusions: Simple hysterectomy is safe and potentially non-inferior to the radical surgery in patients with early-stage cervical cancer ≤2 cm.

Trial registration number: NCT02613286.

Keywords: Cervix Uteri; Gynecologic Surgical Procedures; Hysterectomy; Surgical Procedures, Operative.